Activation of G Proteins Bidirectionally Affects Apoptosis of Cultured Cerebellar Granule Neurons

Guang‐Mei ‐M Yan, Sui‐Zhen ‐Z Lin, Robert P. Irwin, Steven M. Paul

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Abstract

Abstract: Cultured cerebellar granule neurons maintained in depolarizing concentrations of K+ (25 mM) and then switched to physiological concentrations of K+ (5 mM) undergo apoptosis. We now report that activation of specific G proteins robustly and bidirectionally affects apoptosis of cultured rat cerebellar granule neurons. Stimulation of Gs with cholera toxin completely blocks apoptosis induced by nondepolarizing concentrations of K+, whereas stimulation of Go/Gi with the wasp venom peptide mastoparan induces apoptosis of cerebellar granule neurons even in high (depolarizing) concentrations of K+. Moreover, pretreatment of cerebellar granule neurons with cholera toxin attenuates neuronal death induced by mastoparan. By contrast, pertussis toxin, cell‐permeable analogues of cyclic AMP, and activators of protein kinase A do not affect apoptosis of cultured cerebellar granule neurons. These data suggest that G proteins may function as key switches for controlling the programmed death of mammalian neurons, especially in the developing CNS.

Original languageEnglish
Pages (from-to)2425-2431
Number of pages7
JournalJournal of Neurochemistry
Volume65
Issue number6
DOIs
StatePublished - Dec 1995

Keywords

  • Apoptosis
  • Cerebellar granule neurons
  • Cholera toxin
  • G proteins
  • Mastoparan
  • Pertussis toxin
  • Programmed cell death

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